HCV is a positive-strand RNA virus and belongs to the genus Hepacivirus of the Flaviviridae family, and it has been identified to have at least six major genotypes and comprises more than 50 subtypes. The single strand HCV RNA genome is approximately 9500 nucleotides in length and has a single open reading frame (ORF) encoding a single large polyprotein of approximately 3000 amino acids. In infected cells, this polyprotein is cleaved by cellular and viral proteases at multiple sites, resulting in structural and non-structural (NS) proteins. In the case of HCV, the formation of mature non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B) is achieved by two viral proteases.
A treatment regimen for chronic HCV infection comprises: peginterferon-α in combination with ribavirin for treating HCV-infected patients and patients with cirrhotic. If the treatment fails, the treatment regimen including interferon is used again, and the sustained virological response rate will be as low as 14%. In addition, the treatment regimen including interferon has increased toxic side effects in patients with cirrhotic.
With the development of HCV NS3/4A protease inhibitors, NS5A inhibitors and NS5B polymerase inhibitors, as new therapies, the use of interferon and ribavirin is not required, which not only reduces toxicity but also shortens treatment duration. These new classes of inhibitors include ABT-267 (WO2010144646), ABT-530 (WO2012051361), etc.